By a News Reporter-Staff News Editor at Drug Week -- Investigators publish new report on Liver Diseases and Conditions. According to news reporting originating in Dortmund, Germany, by NewsRx journalists, research stated, "In previous studies we identified the interferon stimulated gene 15 (ISG15) as a pro-viral host factor in the pathogenesis of hepatitis C virus (HCV) infection. However, the functional link between ISG15 and the HCV replication cycle is not well understood."
The news reporters obtained a quote from the research from Institute for Analytical Sciences, "Aim of the present study was to functionally analyze the role of ISG15 and to identify possible HCV promoting effector molecules. Isg15 suppression was investigated in the murine subgenomic HCV replicon (MH1) transfected with Isg15-specific siRNA and in C57BL/6 mice intravenously injected with lipid nanoparticles (LNP)-formulated siRNA. Interestingly, the LNP-formulated siRNA led to hepatocyte-specific knockdown of Isg15 in vivo, which mediated a hypo-responsiveness to endogenous and exogenous interferon. A label free proteome analysis accompanied by western blot and quantitative RT-PCR techniques led to identification of five candidate proteins (Heterogeneous nuclear ribonucleoprotein A3 (HnrnpA3), Heterogeneous nuclear ribonucleoprotein K (HnrnpK), Hydroxymethylglutaryl-CoA synthase (Hmgcs1), Isocitrate dehydrogenase cytoplasmic (Idh1) and Thioredoxin domain-containing protein 5 (Txndc5)) that are either involved in lipid metabolism or belong to the family of Heterogeneous nuclear ribonucleoprotein (Hnrnp). All candidate proteins are likely to be associated with the HCV replication complex. Furthermore treatment with HnrnpK-specific siRNA directly suppressed HCV replication in vitro."
According to the news reporters, the research concluded: "Taken together these data suggest that targeting Isg15 may represent an attractive novel therapeutic option for the treatment of chronic HCV infection."
For more information on this research see: Identification of proteins that mediate the pro-viral functions of the interferon stimulated gene 15 in hepatitis C virus replication. Antiviral Research, 2013;100(3):654-661. Antiviral Research can be contacted at: Elsevier Science Bv, PO Box 211, 1000 Ae Amsterdam, Netherlands. (Elsevier - www.elsevier.com; Antiviral Research - www.elsevier.com/wps/product/cws_home/521852)
Our news correspondents report that additional information may be obtained by contacting C.I. Real, Leibniz Inst Analyt Sci ISAS, D-44227 Dortmund, Germany. Additional authors for this research include D.A. Megger, B. Sitek, K. Jahn-Hofmann, L.M. Ickenstein, M.J. John, A. Walker, J. Timm, K. Kuhlmann, M. Eisenacher, H.E. Meyer, G. Gerken, R. Broering and J.F. Schlaak (see also Liver Diseases and Conditions).
Keywords for this news article include: HCV, Viral, Europe, Germany, Dortmund, Virology, Cytokines, Treatment, Hepatology, Amino Acids, Interferons, RNA Viruses, Carrier Proteins, Gastroenterology, Hepatitis C Virus, Virus Replication, Infectious Disease, RNA-Binding Proteins, Flaviviridae Infections, Digestive System Diseases, Microbiological Processes
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